Lipoproteins & Hyperlipidemias

Question 1

Lipoprotein (a) / Lp(a)

Answer 1

similar to LDL but w/ additional apo(a)
structure of “kringles”

covelantly linked to apo B-100 via disulfide bonds (sturtural analog to plasminogen)

Apo(a) comepte with plasminogen binding to fibrin -> decreased removal -> increased blood clots

could trigger MI/stroke

Question 2

Coronary Heart Disease Risk Factors

Answer 2

• cholesterol/HDL ratio >5
• LDL/HDL ratio HIGH
• TAG/HDL ratio >4

Question 3

oxLDL

Answer 3

formed form LDL by oxidation of phospholipids or apo B-100

Formation is

Activated
-superoxide, nitric oxide (NO), hydrogen peroxide, other oxidants

Inhibited
-Ascorbic acid, B-carotene, antioxidants

attach to macrophages via SR-A (converts to foam cell)
fibrofatty atheroma & fatty streaks
oxLDL accumulates (not recognized by LDL receptor) plaque formation

Question 4

LDL (A/B)

Answer 4

• LDL A is large & less dense
• LDL B (bad news) small &dense
• penetrates endothelium
• retained by ECM & proteoglycans
• can be oxidized to oxLDL
• risk factor for CHD

Question 5

Hypoalphalipoproteinemia

Answer 5

Low serum HDL

obesity, smoking, cholesterol reducing drugs

Question 6

Tangier disease

Answer 6

hereditary

Low serum HDL (coronary heart disease in childhood)

orange tonsils, corneal opacities, hepatosplenmegaly

defective cholesterol ABC transporter
less substrate for LCAT
early degen of apo-A1

Question 7

Abetalipoproteinemia

Answer 7

rare

Low serum VLDL, LDL, CM
defect in microsomal TAG transfer protein (MTP)
- needed for formation of VLDL or CM (w interaction of apo B)
-fat malabsorption
-TAG accumulates in liver & intstine
-retinitis pigmentosa
-peripheral neuropathy

Question 8

Hypertriacylglycerolemia

Answer 8

• lipoproteins with high TAGs
• reduced LPL
• defective apo-CII
• increase release of VLDL

associations

• hyperstension
• untreated diabetes mellitus
• oral contraceptives
• hyperuricemia

Question 9

Hypercholesterolemia

Answer 9

• high lipoproteins, cholesterol, cholesteryl esters (LDL/lipoprotein remnants)
• Defective LDL receptors
• apo E deficiency

associations

• hypothyrodism
• nephrotic syndrome
• obstructive liver disease
• treatment with specific drugs

Question 10

Type I: Hyperchylomicronemia

Answer 10

-high CM (after 12-14 hr fast)
-genetic deficiency of LPL or apo-CII
childhood
-Xanthomas on trunk, butt, extemities
-creamy layer on top of blood vial

• lipemia retinalis
• hepatosplenomegaly
• irritability
• reccurent epigastric pain
• increased risk of pancreatitis

Question 11

Type IIa: Familial Hypercholesterolemia

Answer 11

High LDL, Normal VLDL

autosomal dominant

• heterozygous 1:5000 (adult onset, risk of CHD)
• homozygous 1:1 million (child onset, MI, death)

Defective LDL receptor

Xanthoma over tendon and xanthelasmas

Treated with Statins

Question 12

Type IIb: Familial Combined Hyperlipidemia

Answer 12

onset of puberty (1:10)

High LDL & VLDL

very complex (several genes)

Question 13

Type III: Dysbetalipoproteinemia (rare)

Answer 13

High IDL & CM remnants
Apo-E deficiency

homozygous for apo-E2
similar blood cholesterol to IIa/b
TAG serum level can be elevated

palmar xanthomas over elbows and knees 
adult onset (accelerated athersclerosis)

Question 14

Type IV: Hyperprebetalipoproteinemia

Answer 14

• High serum VLDL
• LPL deficiency OR over-produciton of VLDL
• High TAG -> pancreatits

Question 15

Type V: Mixed Hypertriacyglycerolemia

Answer 15

High serum VLDL & CM

creamy layer on top of serum